Siekmeier Rüdiger, Grammer Tanja, März Winfried
Federal Institute for Drugs and Medical Devices Bonn, Germany.
J Cardiovasc Pharmacol Ther. 2008 Dec;13(4):279-97. doi: 10.1177/1074248408326488. Epub 2008 Oct 22.
Vascular endothelium plays a crucial role in ensuring normal function and morphology of blood vessels, and many risk factors of atherosclerosis act via their effects on endothelial cells. However, endothelial dysfunction is induced by very different pathomechanisms. In principle, it is caused by an impaired bioavailability of nitric oxide (NO) due to an inhibited synthesis (eg, by asymmetric dimethylarginine [ADMA]) or increased consumption of formed NO (by reactive oxygen species [ROS]). ROS can be synthesized in the organism (eg, by different enzymes) or can be administered from the environment (eg, by cigarette smoking), whereas ADMA is the subject of endogenous metabolism only. Many studies have elucidated the system of pathomechanisms and targeted some as potential goals for therapeutic interventions. This review demonstrates roles of ROS, NO, ADMA, endothelin, and estrogen in endothelial function and dysfunction focusing on homocysteinemia and diabetes mellitus and provide examples for the medical treatment of endothelial dysfunction.
血管内皮在确保血管的正常功能和形态方面发挥着关键作用，动脉粥样硬化的许多危险因素通过对内皮细胞的作用来发挥影响。然而，内皮功能障碍是由非常不同的病理机制诱导的。原则上，它是由于一氧化氮（NO）生物利用度受损所致，这是由于合成受到抑制（例如，被不对称二甲基精氨酸[ADMA]抑制）或生成的NO消耗增加（被活性氧[ROS]消耗）。ROS可在生物体内合成（例如，由不同的酶合成）或可从环境中摄入（例如，通过吸烟摄入），而ADMA仅是内源性代谢的物质。许多研究已经阐明了病理机制系统，并将其中一些作为治疗干预的潜在目标。本综述阐述了ROS、NO、ADMA、内皮素和雌激素在内皮功能和功能障碍中的作用，重点关注高同型半胱氨酸血症和糖尿病，并提供内皮功能障碍药物治疗的实例。
